Angina, clinical trials with

Coronary events Angina, Ml, cardiac arrest, and /or sudden death have been reported during clinical trials with apomorphine. Use extra caution in prescribing apomorphine for patients with known cardiovascular and cerebrovascular disease. Sulfite Apokyn (apomorphine) contains metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes. 

Table 3.1 Folic acid, Bg, B12 and cardiovascular outcomes. This table summarizes all the important double-blind randomized clinical trials with the use of folie acid, Bg and B12 vitamins for cardiovascular disease prevention. 5-MTHF 5-methyl tetrahydrofolate CKD chronic kidney disease CVD cardiovascular disease DVT deep vein thrombosis ESRD end stage renal disease FA folic acid f/u follow-up MI myocardial infarction RR relative risk UA unstable angina.

Dobutamine (76), on the other hand, is a dopamine derivative which does not act centrally, but is of interest because of its coronary vasodilator properties. Such drugs are potentially of value in treatment of angina pectoralis. Further, it is now undergoing extensive clinical trials as an inotropic agent for use in heart failure. Its synthesis is effected by Raney nickel catalyzed reduction of methyl p-methoxyvinylphenylketone (75) to its dihydro analog followed by reductive alkylation with p-(3,4-dimethoxyphenyl)ethylamine. The ether groups are cleaved with HBr to complete the synthesis of... 

Nitrate-free interval Several clinical trials of nitroglycerin in patients with angina pectoris have evaluated regimens that incorporated a 10- to 12-hour nitrate-free interval. 

In clinical practice, nitrates are used on a large scale in the treatment of ischaemic heart disease, in particular stable angina. Although very effective as a symptomatic measure, it remains unclear so far whether the prognosis of patients with stable angina is improved by nitrate treatment. Clinical trials addressing this question are ungoing. 

Toxicities include elevation of liver enzymes with some risk of liver damage, renal impairment, and teratogenic effects. A low frequency of cardiovascular effects (angina, tachycardia) was reported in clinical trials of leflunomide. 

Patients with acute coronary syndromes such as acute myocardial infarction and unstable angina remain at risk for recurrent myocardial ischemia despite therapy with antiplatelet agents and heparin. Although first clinical trials indicate a possible use of oral direct TIs for the prevention of cardiovascular events in patients after acute myocardial infarction, the presently available data are still limited and it has not... 

Several clinical trials for therapeutic angiogenesis have been conducted in patients with myocardial ischemia. Although an improvement in exercise time, angina class, and quality of life was observed in placebo and VEGF-delivered groups, there was no significant difference between treated patients and controls. 

Chabaud, S. Girard, P. Nony, P. Boissel, J.P. Clinical trial simulation using therapeutic effect modeling application to ivabradine efficacy in patients with angina pectoris. J. Pharmacokinet. Pharmacodyn. 2002, 29 (4), 339-363. Minto, C.F. Schnider, T.W. Shafer, S.L. Pharmacokinetic and pharmacodynamics of remifentail. II. Model application. Anesthesiology 1997, 86 (1), 24-33. 

The interpretation of these sporadic cases is controversial, although some have argued that the reported cardiovascular adverse effects occur more often with sildenafil than with other pharmacological treatments of erectile dysfunction. It is at present unclear whether there is an increased risk with sildenafil. For example, in placebo-controlled trials there have been no differences in the incidences of myocardial infarction, angina, or coronary artery disorders between sildenafil and placebo (9). Exclusion criteria in clinical trials may have prevented the inclusion of patients who are at increased risk of adverse events. On the other hand, sexual activity itself increases cardiac workload and the risk of myocardial infarction. Patients with cardiovascular disease should be cautious in their use of sildenafil. 

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